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The goal of this study was to identify novel factors that mediate skeletal muscle development or function. We began the study by searching the gene expression databases for genes that have no known functions but are preferentially expressed in skeletal muscle. This search led to the identification of the Src homology three (SH3) domain and cysteine rich (C1) domain 3 ( Stac3)  gene. We experimentally confirmed that  Stac3  mRNA was predominantly expressed in skeletal muscle. We determined if  Stac3  plays a role in skeletal muscle development or function by generating  Stac3  knockout mice. All  Stac3  homozygous mutant mice were found dead at birth, were never seen move, and had a curved body and dropping forelimbs. These mice had marked abnormalities in skeletal muscles throughout the body, including central location of myonuclei, decreased number but increased cross-sectional area of myofibers, decreased number and size of myofibrils, disarrayed myofibrils, and streaming Z-lines. These phenotypes demonstrate that the  Stac3  gene plays a critical role in skeletal muscle development and function in mice.

Stac3 Is a Novel Regulator of Skeletal Muscle Development in Mice